Oncology describes the diagnosis, research, and treatment of cancer, a large group of diseases bound together by the rapid creation of abnormal cells that grow beyond physiological constraints. World Health Organization statistics show that in 2020, nearly 10 million people worldwide died from cancer and 20 million new cancer cases were diagnosed.
Cancer is governed by the behaviors and interactions of numerous distinct cell types, which are mediated by a vast number of protein signaling pathways. However, while mutant gene products lead to altered pathway function, ultimately leading to oncogenesis, the precise underlying mechanisms and potential protein-level therapeutic targets remain unclear. The growing field of “structural oncology” seeks to characterize how mutations affect protein structures and conformations to identify their impact on signaling pathways and function.
Many anticancer therapeutic approaches target membrane receptors. Determining how therapeutic agents interact with receptor structures is important for understanding drivers of drug efficacy and potential synergistic relationships. For example, in breast cancer both trastuzumab and pertuzumab reduce cellular growth by inhibiting human epidermal growth factor receptor 2 (HER2). When used together, these drugs have a documented synergistic effect. Structural biology lets you directly visualize these protein complexes to determine their binding and interaction mechanisms, leading to key insights for the design of bispecific molecules with potentially greater clinical efficacy.
Structural biology has historically used X-ray crystallography for protein characterization, which necessitates crystallization, a laborious process that often requires researchers to extensively alter the protein of interest. Cryo-electron microscopy (cryo-EM) lets scientists observe biomolecules in their native state, without the need for crystallization or other special preparations. This lets researchers capture complete and fully functional macromolecular complexes in different conformations and functional states. Researchers have found cryo-EM particularly useful for investigating membrane proteins, which account for over 60% of drug targets and have properties that make them challenging to crystalize.
Oncology research with cryo-EM
With cryo-EM, structural biologists can study the structures of proteins, including membrane receptors and other biomolecules, which previously could not be imaged using X-ray crystallography techniques. Cryo-EM allows researchers to freeze biomolecules in different conformations and visualize protein interactions. With structural insights, scientists can better understand conditions for cancer cell growth and identify new ways to treat cancer.
Download the "Understanding the complexity of cancer with cryo-EM" eBook to learn how:
- Cryo-EM can help find the molecular drivers of cancer
- Protein mechanisms can be characterized for cancer research
- Membrane receptor structures are important in drug discovery